The application of positron emission tomography (PET) to the study of human tumors and to the study of the response of such tumors to different therapeutic approaches continues to be of interest. Of particular interest are studies where valid tracer kinetic models exist and physiological quantitation is possible. Such kinetic models are the result of a thorough understanding of the biochemistry of the tracer in the tumor and in the surrounding tissue.
Polyamines have been investigated for use as biochemical markers for malignancy, including brain tumors. Since adult brain parenchyma does not normally divide, a polyamine that marks cell growth and proliferation should be taken up and metabolized solely by the brain tumor. Volkow, et al. [Science, 221, 673 (1983)] tested the feasibility of using the polyamine putrescine, labeled with [.sup.3 H] and [.sup.14 C], as a PET tracer for brain tumors. They found that in vivo uptake into transplanted rat glioma was 35 times greater than in normal brain tissue and that metabolism to spermine by the tumor was rapid, in contrast to adjacent normal brain tissue. Winstead, et al. [Eur. J. Nucl Med., 5, 165 (1980)] synthesized carbon-11 labeled putrescine, but the synthesis yielded only carrier contaminated material that had too low a specific activity to be acceptable for human studies.
Studies such as the Volkow, et al. study showed the usefulness of the putrescine model but also showed that because of impurities, very low specific activity, inappropriate half-lives, or non-optimum radiation emission, the carrier-added-[.sup.11 C], the [.sup.3 H] and the [.sup.14 C] radiolabels were not suitable for the preparation of a tracer for human studies of brain tumors using PET.
One purpose of the present invention is to overcome these deficiencies of the prior art by providing a no-carrier-added [.sup.11 C]-labeled putrescine material that is a useful tracer when used with PET for quantitating the degree of malignancy in vivo and for monitoring response to radio- and chemotherapy.
Another purpose of the present invention is to provide a synthesis of the no-carrier-added [1-.sup.11 C]putrescine in sufficiently high purity and specific activity to avoid significantly perturbing the plasma concentration of the endogenous diamine.